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PDBsum entry 4bbh
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PDB id:
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Transferase
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Title:
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Plasmodium vivax n-myristoyltransferase with a bound benzothiophene inhibitor
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Structure:
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Glycylpeptide n-tetradecanoyltransferase. Chain: a, b, c. Engineered: yes
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Source:
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Plasmodium vivax. Organism_taxid: 5855. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss.
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Resolution:
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1.63Å
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R-factor:
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0.217
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R-free:
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0.264
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Authors:
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M.D.Rackham,J.A.Brannigan,D.K.Moss,Z.Yu,A.J.Wilkinson,A.A.Holder, E.W.Tate,R.J.Leatherbarrow
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Key ref:
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M.D.Rackham
et al.
(2013).
Discovery of novel and ligand-efficient inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferase.
J Med Chem,
56,
371-375.
PubMed id:
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Date:
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23-Sep-12
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Release date:
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05-Dec-12
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PROCHECK
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Headers
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References
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A5K1A2
(A5K1A2_PLAVS) -
Glycylpeptide N-tetradecanoyltransferase from Plasmodium vivax (strain Salvador I)
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Seq:
Struc:
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410 a.a.
384 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.3.1.97
- glycylpeptide N-tetradecanoyltransferase.
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Reaction:
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N-terminal glycyl-[protein] + tetradecanoyl-CoA = N-tetradecanoylglycyl- [protein] + CoA + H+
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N-terminal glycyl-[protein]
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+
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tetradecanoyl-CoA
Bound ligand (Het Group name = )
matches with 95.38% similarity
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=
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N-tetradecanoylglycyl- [protein]
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+
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CoA
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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J Med Chem
56:371-375
(2013)
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PubMed id:
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Discovery of novel and ligand-efficient inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferase.
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M.D.Rackham,
J.A.Brannigan,
D.K.Moss,
Z.Yu,
A.J.Wilkinson,
A.A.Holder,
E.W.Tate,
R.J.Leatherbarrow.
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ABSTRACT
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N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A
lead-hopping approach was utilized in the design and synthesis of novel
benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (Pf) and
Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens
NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic
activity in vitro. The binding mode of this series was determined by
crystallography and shows a novel binding mode for the benzothiophene ring.
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